Step 1: Synthesis of 2-chloropyrimidin-5-ylboronic acid
Under argon protection, 5-bromo-2-chloropyrimidine (1.0 g, 5.170 mmol) was dissolved in a solvent mixture of THF and toluene (25 mL, 4:1 v/v), and cooled to -78 °C. n-Butyllithium (1.6 M hexane solution, 3.87 mL, 5.61 mmol) was slowly added dropwise at -78 °C, and the reaction was kept at -78 °C for 4 hours after completion of the dropwise addition. After completion of the reaction, the reaction mixture was diluted with ice water, returned to room temperature and stirred for 1 hour. Subsequently, the aqueous phase was extracted with ether and the organic phase was combined. The aqueous phase was acidified to pH 2-3 with 1N hydrochloric acid and extracted with ethyl acetate. All organic phases were combined, dried with anhydrous sodium sulfate and concentrated under reduced pressure to give 2-chloropyrimidin-5-ylboronic acid (0.6 g, 73.3% yield) as a white solid. Mass spectrum (MS): 159.3 [M+H]+.
